Paclitaxel, a naturally occurring diterpenoid extracted from yew trees, has demonstrated great potential as an anti-cancer drug. It is unique among antimitotic drugs in that it promotes the assembly of stable microtubules from tubulin. It binds strongly to microtubules, thus preventing depolymerization of the tubulin and inhibiting mitosis. The structure of paclitaxel and the numbering system conventionally used is shown below. This numbering system is also applicable to compounds used in the process of the present invention.

Docetaxel, a paclitaxel derivative, has also demonstrated excellent antitumor activity over the past few years. Docetaxel has the following structure:

The chemical conversion of naturally occurring precursors such as 10-deacetylbaccatin III (10-DAB III) and 9-dihydro-13-acetylbaccatin III (9-DHAB III) to paclitaxel and docetaxel have been reported. Because of the congested position of the 13-hydroxy group of 10-DAB-III and 9-DHAB-III, acylation with β-lactam has become the method of choice for acylation of that position. An example of β-lactam which has been extensively used in the synthesis of paclitaxel and docetaxel is shown below:
where G is a benzoyl group when preparing paclitaxel or a tert-butyloxycarbonyl (t-BOC) group when preparing docetaxel and P is a “classical” hydroxy protecting group such as TES, methyloxypropyl and 2,2,2-trichloroethoxycarbonyl.
An important limitation of the current method is that although the syn lactam can be obtained by methods such as the Staudinger reaction, the racemic form is always produced. The racemic mixture must be submitted to a kinetic resolution either prior to or during coupling with baccatin III. In either case half of the lactam material must be discarded. A chiral synthesis of β-lactams would produce the desired isomer stereoselectively but few such synthetic routes have been developed.
It would thus be highly desirable to be provided with new routes for the enantioselective production of chiral β-lactams and new methods to use such β-lactams in the synthesis of paclitaxel, docetaxel and other biologically active taxanes.